Dry powder composition comprising long-chain RNA

Abstract

The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

The invention claimed is: 
     
       1. A dry powder composition comprising a long-chain RNA molecule comprising at least 30 nucleotides in a complex with a cationic or polycationic compound, wherein said dry powder:
 (i) has a residual moisture content of less than 7% (w/w); and 
 (ii) comprises a plurality of particles having a median particle size, in a volume weighted distribution of the composition, in a range from 1 μm and 20 μm. 
 
     
     
       2. The dry powder composition according to  claim 1 , wherein the average sphericity of the particles in the composition is in a range from 0.7 to 1.0. 
     
     
       3. The dry powder composition according to  claim 1 , wherein the composition has a residual moisture content of 5% (w/w) or less. 
     
     
       4. The dry powder composition according to  claim 1 , wherein the long-chain RNA molecule is present in the form of a free long-chain RNA molecule, or in the form of a complex comprising the long-chain RNA molecule. 
     
     
       5. The dry powder composition according to  claim 1 , wherein the long-chain RNA molecule is in a complex with a cationic or polycationic lipid. 
     
     
       6. The dry powder composition according to  claim 1 , wherein the long-chain RNA molecule is a single-stranded RNA molecule. 
     
     
       7. The dry powder composition according to  claim 1 , wherein the long-chain RNA molecule comprises at least one open reading frame (ORF) encoding a protein or a peptide. 
     
     
       8. The dry powder composition according to  claim 7 , wherein the long-chain RNA molecule is an mRNA molecule. 
     
     
       9. The dry powder composition according to  claim 7 , wherein the long-chain RNA molecule comprises at least 200 nucleotides. 
     
     
       10. The dry powder composition according to  claim 9 , wherein the long-chain RNA molecule comprises at least one modification. 
     
     
       11. The dry powder composition according to  claim 9 , wherein the dry powder composition comprises at least one excipient. 
     
     
       12. The dry powder composition according to  claim 9 , wherein the dry powder is made by a method of spray-drying. 
     
     
       13. The dry powder composition according to  claim 12 , wherein the method of spray-drying comprises the steps of:
 (a) providing a liquid comprising the long-chain RNA molecule to be spray-dried; and 
 (b) spray-drying the liquid of step (a) with a spray-drying device having a drying gas inlet and a drying gas outlet, wherein the drying gas has a temperature at the inlet of at least 85° C., wherein the drying gas has a temperature at the outlet of at least 50° C. 
 
     
     
       14. The dry powder composition according to  claim 11 , wherein the at least one excipient selected from a cryoprotectant, a lyoprotectant, and a bulking agent. 
     
     
       15. The dry powder composition according to  claim 13 , wherein the liquid of step (a) comprises a spray-drying-compatible solvent. 
     
     
       16. The dry powder composition according to  claim 13 , wherein the liquid of step (a) is atomized and a droplet resulting from the atomization of the liquid is characterized by a mass median aerodynamic diameter of 300 nm to 200 μm. 
     
     
       17. The dry powder composition according to  claim 13 , wherein the liquid of step (a) further comprises a suspending agent and/or osmolality of about 200 mosmol/l to about 400 mosmol/l. 
     
     
       18. A pharmaceutical composition comprising the dry powder composition according to  claim 9 . 
     
     
       19. The pharmaceutical composition according to  claim 18 , further comprising at least one pharmaceutically acceptable excipient. 
     
     
       20. The pharmaceutical composition according to  claim 18 , wherein the dry powder is formulated for administration by inhalation. 
     
     
       21. The pharmaceutical composition according to  claim 18 , wherein the dry powder is formulated for pulmonary delivery. 
     
     
       22. The dry powder composition according to  claim 9 , wherein upon reconstitution of the dry powder in a suitable solvent, the complexed long-chain RNA molecule is present in the solvent in the form of nanoparticles having a size of about 50 to 500 nm. 
     
     
       23. The dry powder composition according to  claim 14 , wherein the at least one excipient comprises a free carbohydrate. 
     
     
       24. The dry powder composition according to  claim 23 , wherein the at least one excipient comprises lactose, sucrose or trehalose. 
     
     
       25. The dry powder composition according to  claim 9 , wherein the long-chain RNA molecule is 500 to 20,000 nucleotides in length.